Synaptotagmin IV: Biochemistry, genetics, behavior, and possible links to human psychiatric disease

Authors: Ferguson, Gregory¹; Vician, Linda¹; Herschman, Harvey²

Source: Molecular Neurobiology, Volume 23, Numbers 2-3, April 2001 , pp. 173-185(13)

Buy & download fulltext article:

Price: $42.00 plus tax (Refund Policy)

Abstract:

We isolated the rat synaptotagmin IV (Syt IV) cDNA in a screen for sequences that are specifically induced in neuronal cells. The Syts are a large family of genes thought to mediate synaptic function. Syt IV is brain-specific, induced in hippocampus by depolarization, and predominantly vesicular. To assess the function role of Syt IV in vivo, we generated Syt IV (−/−) mutant mice. Syt IV (−/−) mice are viable and appear normal, indicating this gene is not essential for survival or gross development. However, Syt IV (−/−) mutants, when compared to wild-type littermates, have deficits in fine motor coordination and hippocampus-dependent memory, suggesting Syt IV has a role in normal brain function. The human Syt IV ortholog maps to a region of chromosome 18 previously associated with the human psychiatric disorders, schizophrenia and bipolar disease. These results suggest that Syt IV is required in certain types of neurons for optimal functionality, that perturbations in the levels of Syt IV can result in memory loss in mice, and that Syt IV alterations may lead to psychiatric disease in humans.

Keywords: Synaptotagmin IV; depolarization-inducible; synaptic plasticity; learning and memory; hippocampus; schizophrenia

Document Type: Research article

DOI: http://dx.doi.org/10.1385/MN:23:2-3:173

Affiliations: 1: Department of Biological Chemistry, University of California, Los Angeles, 90095, Los Angeles, CA, 2: Department of Biological Chemistry, University of California, Los Angeles, 90095, Los Angeles, CA, Email: HHerschman@MEDNET.ucla.edu

Publication date: 2001-04-01